Multi-color magnetic particle imaging for cardiovascular interventions.
Magnetic particle imaging (MPI) uses magnetic fields to visualize the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIOs). Guidance of cardiovascular interventions is seen as one possible application of MPI. To safely guide interventions, the vessel lumen as well as all required interventional devices have to be visualized and be discernible from each other. Until now, different tracer concentrations were used for discerning devices from blood in MPI, because only one type of SPIO could be imaged at a time. Recently, it was shown for 3D MPI that it is possible to separate different signal sources in one volume of interest, i.e. to visualize and discern different SPIOs or different binding states of the same SPIO. The approach was termed multi-color MPI. In this work, the use of multi-color MPI for differentiation of a SPIO coated guide wire (Terumo Radifocus 0.035″) from the lumen of a vessel phantom filled with diluted Resovist is demonstrated. This is achieved by recording dedicated system functions of the coating material containing solid Resovist and of liquid Resovist, which allows separation of their respective signal in the image reconstruction process. Assigning a color to the different signal sources results in a differentiation of guide wire and vessel phantom lumen into colored images.


Revision of the cricket genus Cardiodactylus (Orthoptera, Eneopterinae, Lebinthini): the species from both sides of the Wallace line, with description of 25 new species.
The genus Cardiodactylus is the most speciose and widely distributed genus of the cricket subfamily Eneopterinae and of the Lebinthini tribe. Along with diverse acoustic features, this genus is also characterized by a wide distribution area running from Japan to Southeast Asia, Northern Australia and in many archipelagos in the Western Pacific, with a high contrast in species distributions. In this paper we start revising Cardiodactylus by focusing on the western region of its wide distribution and the Novaeguineae species group. We describe 25 new species of Cardiodactylus, redescribe 3 species and bring new signalizations for 5 species. Whenever possible, information is provided about species distribution, male calling song and male and female genitalia, forewing venation and habitat.


Factors related to motivation, organisational climate and work engagement within the practice environment of nurse practitioners in the Netherlands.
To explore motivation, organisational climate, work engagement and related factors within the practice environment of nurse practitioners. Motivation in the workplace, organisational climate and work engagement are important to motivate nurse practitioners and prevent early exit. However, little is known about related factors. A cross-sectional design using a digital survey with multiple-choice and open-ended questions. Data were collected from 1 November 2019 to 30 March 2020. The survey contained demographic and job-related data, instruments on motivation in the workplace, organisational climate and work engagement. Three open-ended questions were added to invite respondents to tell about their next career step, (dis)satisfaction with salary and additional comments. Quantitative data were not normally distributed (Kolmogorov-Smirnov test). Kruskal Wallis tests and Mann-Whitney U tests were used to test the relationship between independent and dependent variables. Answers on the open-ended questions were coded and categorised in themes. The STROBE checklist was followed. In total 586 questionnaires were completed. The majority of the respondents were female (85%), and their mean age was 47 years (range 26-66 years). Aged 45 or over, more work experience, working in nursing homes, experiencing more autonomy, collaboration with other nurse practitioners, a firmly anchored position, satisfaction with salary and developmental opportunities contributed positively to the practice environment. Answers on the open-ended questions supported the quantitative results. Work motivation, organisational climate and work engagement are positively related to a large variety of personal and work-related factors. Therefore, policymakers and professional organisations should be aware of the impact of these influencing factors to enhance an inspiring work environment. Awareness of factors that influence nurse practitioners' practice environment can be used as a tool to screen and improve the present work environment.


Cellular Na+ handling mechanisms involved in airway smooth muscle contraction (Review).
A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization. Na+ plays an important role in preserving the resting membrane potential; this ion is extracted from the cells by the Na+/K+ ATPase (NKA) or introduced into the cytoplasm by the Na+/Ca2+ exchanger (NCX). During depolarization, Na+ appears to accumulate in specific regions beneath the plasma membrane, generating local concentration gradients which determine the handling of Ca2+. At rest, the smooth muscle has a basal tone that is preserved by the continuous adjustment of intracytoplasmic concentrations of Ca2+ and Na+. At homeostasis, the Na+ concentration is primarily dependent on three structures: the NKA, the NCX and non-specific cation channels (NSCC). These three structures, their functions and the available evidence of the probable role of Na+ in asthma are described in the present review.


Neutral detergent fiber increases endogenous ileal losses but has no effect on ileal digestibility of amino acids in growing pigs.
Two experiments were conducted to determine the effect of neutral detergent fiber (NDF) on endogenous amino acids and protein ileal losses; and also apparent ileal digestibility (AID), and standardized ileal digestibility (SID) of amino acids and crude protein. Sixteen barrows were fed four protein-free diets containing graded NDF levels in Experiment 1. NDF was a mixture of sugarcane bagasse and corn leaves (SBCL). Twenty-four barrows were fed diets with soybean protein concentrate (SPC) or casein as protein sources and SBCL or corncobs (CC) as NDF sources in Experiment 2. In Experiment 1, a linear increase (P < 0.05) in endogenous amino acid and protein ileal losses was observed with increased NDF levels, except for arginine, histidine, methionine and proline. In Experiment 2, protein (P < 0.001) and NDF (P < 0.01) sources significantly affected AID of dry matter, which was higher in casein diets (71.7%) and CC diets (70.7%). Protein and NDF sources significantly affected (P < 0.05) SID of crude protein, which was higher in casein diets (92.8%) and CC diets (92.7%). NDF source had no effect (P > 0.05) on SID of amino acids. Overall, this study showed that NDF increased endogenous amino acid and protein ileal losses, but did not affect ileal digestibility of amino acids.


Cancer Stem Cells and Anti-tumor Immunity.
Cancer stem cells (CSCs) are correlated with poor clinical outcomes due to their contribution to chemotherapy resistance and the formation of metastasis. Multiple cell surface and enzymatic markers have been characterized to identify CSCs, which is important for diagnosis, therapy, and prognosis. This review underlines the role of CSCs and circulating tumor cells (CTCs) in tumor relapse and metastasis, the characteristics of CSC and CTC biomarkers, and the techniques used to detect these cells. We also summarized novel therapeutic approaches toward targeting CSCs, especially focusing on the role of immune checkpoint blockades (ICB), such as anti-programmed death 1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PDL1) therapies. Additionally, we address an intriguing new mechanism of action for small molecular drugs, such as telomere-targeted therapy 6-thio-2'deoxyguanosine (6- thio-dG), and how it reshapes tumor microenvironment to overcome ICB resistance. There are indications, that personalized cancer therapy targeting CSC populations in conjunction with immune-mediated strategy hold promise for the removal of residual therapy-resistant CSCs in the near future.


The occupational health audit.
The final report contains no magic or proprietary secrets. It is simply a logical review of what exists with an orderly recommendation of what should be done. To repeat -- many times the hardest part of any job is getting started. The purpose of this exercise is to provide a plan and a way to get started. This may seem like something so obvious that it is not needed. But a review of existing occupational health programs dispels that view. Five years after the enactment of the Occupational Safety and Health Act of 1970, hundreds of thousands of physical examinations are still being performed in a total vacuum; examinations whose contents bear little relationship to the hazards encountered. Countless laboratory determinations are being provided to personnel officers and plant managers who have absolutely no background in interpreting the meaning of those results. Millions of records are being meticulously kept with no goal in mind as to what purpose they should serve nor consideration for the privacy of individuals. In short, untold millions of dollars are being wasted while the things that should be done are left undone because, to quote, "the cost is too high." Often health professionals are employed by an organization because health crises have developed which force expert handling. The health professional enters chaos and is kept so busy answering fire-calls that there is no time for the orderly evaluation of needs and the development of operating routines required to prevent new crises from developing. Today's crises are being addressed while tomorrow's crises are developing out of routine situations. The health professional is not at fault; rather, executive management has failed to provide the necessary systems to meet its responsibilities. So long as this situation prevails, there is a need for someone to take the time to develop an orderly approach to occupational health surveillance. When such a condition exists, it is time to call in an independent auditor to provide an objective evaluation of what needs to be done. It is to provide a "handle" for getting hold of such situations that we developed our Occupational health Audit. It offers one way to get the job started.


Plant phytochrome B is an asymmetric dimer with unique signalling potential.
Many aspects of plant photoperception are mediated by the phytochrome (Phy) family of bilin-containing photoreceptors that reversibly interconvert between inactive Pr and active Pfr conformers1,2. Despite extensive biochemical studies, full understanding of plant Phy signalling has remained unclear due to the absence of relevant 3D models. Here we report a cryo-electron microscopy structure of Arabidopsis PhyB in the Pr state that reveals a topologically complex dimeric organization that is substantially distinct from its prokaryotic relatives. Instead of an anticipated parallel architecture, the C-terminal histidine-kinase-related domains (HKRDs) associate head-to-head, whereas the N-terminal photosensory regions associate head-to-tail to form a parallelogram-shaped platform with near two-fold symmetry. The platform is internally linked by the second of two internal Per/Arnt/Sim domains that binds to the photosensory module of the opposing protomer and a preceding 'modulator' loop that assembles tightly with the photosensory module of its own protomer. Both connections accelerate the thermal reversion of Pfr back to Pr, consistent with an inverse relationship between dimer assembly and Pfr stability. Lopsided contacts between the HKRDs and the platform create profound asymmetry to PhyB that might imbue distinct signalling potentials to the protomers. We propose that this unique structural dynamism creates an extensive photostate-sensitive surface for conformation-dependent interactions between plant Phy photoreceptors and their signalling partners.


Modeling experimental recordings of vagal afferent signaling of intestinal inflammation for neuromodulation.
Artificial modulation of peripheral nerve signals (neuromodulation) by electrical stimulation is an innovation with potential to develop treatments that replace or supplement drugs. One function of the nervous system that can be exploited by neuromodulation is regulation of disease intensity. Optimal interfacing of devices with the nervous system requires suitable models of peripheral nerve systems so that closed-loop control can be utilized for therapeutic benefit. We use physiological data to model afferent signaling in the vagus nerve that carries information about inflammation in the small intestine to the brain. The vagal nerve signaling system is distributed and complex; however, we propose a class of reductive models using a state-space formalism that can be tuned in a patient-specific manner. These models provide excellent fits to a large range of nerve recording data but are computationally simple enough for feedback control in implantable neuromodulation devices.


A containerless levitation setup for liquid processing in a superconducting magnet.
Containerless processing of materials is considered beneficial for obtaining high quality products due to the elimination of the detrimental effects coming from the contact with container walls. Many containerless processing methods are realized by levitation techniques. This paper describes a containerless levitation setup that utilized the magnetization force generated in a gradient magnetic field. It comprises a levitation unit, a temperature control unit, and a real-time observation unit. Known volume of liquid diamagnetic samples can be levitated in the levitation chamber, the temperature of which is controlled using the temperature control unit. The evolution of the levitated sample is observed in real time using the observation unit. With this setup, containerless processing of liquid such as crystal growth from solution can be realized in a well-controlled manner. Since the levitation is achieved using a superconducting magnet, experiments requiring long duration time such as protein crystallization and simulation of space environment for living system can be easily succeeded.


Protocol for a quasiexperimental study testing the effectiveness of strengthening growth monitoring and promotion in community clinics for improving the nutritional status of under-two children in rural Bangladesh.
The Government of Bangladesh is implementing growth monitoring and promotion (GMP) through community clinics (CC) to improve the nutritional status of children. However, little primary evidence is available on the effectiveness of GMP when delivered through CCs. We aim to examine the effectiveness of GMP activities strengthened in CCs to improve the nutritional status of children under 2 years of age. This is a quasiexperimental, two-arm, mixed methods study. In the intervention arm, a non-governmental organisation is providing support to strengthen GMP implementation in the 30 CCs. The comparison arm has no intervention to strengthen GMP implementation in the 30 CCs. Study participants will be under-two children and their caregivers, and CC service providers (community healthcare provider, CHCP). We will collect quantitative information on children and mothers' anthropometry, sociodemographic condition, food security, children's feeding practices, morbidity and vaccination history at baseline, and follow them up every third month thereafter for 12 months. We will collect qualitative information on (1) knowledge, skill and practice of CHCPs to implement GMP; (2) mothers/caregivers' perception, knowledge and experience of GMP from CCs; (3) experience and suggestions of programme managers about operational challenges and for improving quality of GMP service delivery; and (4) views of the concerned policy planners to strengthen GMP at the CC level. Qualitative information will be collected through key informant and in-depth interviews at baseline and endline. The primary outcome will be the change observed in length-for-age Z-score of children. A difference-in-difference and linear mixed effects analysis of quantitative data will be done. Thematic analysis will be conducted for qualitative information. Triangulation of data derived from different methods will be carried out. This study received ethical approval from the Institutional Review Board of International Centre for Diarrhoeal Disease Research, Bangladesh, and results will be disseminated via peer-reviewed publications and conference presentations. NCT03824756.


Mortality and morbidity associated with gunshot in raptorial birds from the province of Quebec: 1986 to 2007.
Although raptors have been protected for decades in Quebec they are still regular victims of poaching. The objective of this study was to characterize cases of raptor shootings in Quebec over the last 2 decades. We reviewed clinical files, radiographs, and pathology reports on 4805 free-flying birds of prey admitted to the Faculté de médecine vétérinaire between 1986 and 2007. Evidence of gunshots was detected in 6.4% of the birds. Large species, such as ospreys, turkey vultures, snowy owls, and bald eagles represented the most frequently targeted species. The percentage of shot birds has decreased from 13.4% during 1991 to 1992 to 2.2% in 2006 to 2007. Potential reasons for this trend include a decrease in the presence of firearms in raptor habitats and changes in human attitude towards raptorial birds.


Dynamics of Phosphorus Content in the Water-Sediment Interface of Wetlands in a Mid-Temperature Steppe.
In order to reveal dynamics changes in phosphorus release from the sediments of wetlands in a mid-temperature steppe without external phosphorus input, the relationship between phosphorus content in the overlying water, sediment, and interstitial water was studied using the variables control method. The results showed that, during the incubation period, the content of total phosphorus in the overlying water and the content of total phosphorus in interstitial water both presented in the order of August > September > July. Furthermore, the correlation relationships between phosphorus content in the overlying water, total phosphorus in the interstitial water, and the ratios of sediment Olsen-P to total phosphorus in the interstitial water, indicated that Olsen-P might be a kind of release form of phosphorus - from the sediment to the overlying water of the wetlands in Hulunbeier steppe, without external phosphorus input.


A Survey of the Brassica rapa genome by BAC-end sequence analysis and comparison with Arabidopsis thaliana.
Brassica rapa ssp. pekinensis (Chinese cabbage) is an economically important crop and a model plant for studies on polyploidization and phenotypic evolution. To gain an insight into the structure of the B. rapa genome we analyzed 12,017 BAC-end sequences for the presence of transposable elements (TEs), SSRs, centromeric satellite repeats and genes, and similarity to the closely related genome of Arabidopsis thaliana. TEs were estimated to occupy 14% of the genome, with 12.3% of the genome represented by retrotransposons. It was estimated that the B. rapa genome contains 43,000 genes, 1.6 times greater than the genome of A. thaliana. A number of centromeric satellite sequences, representing variations of a 176-bp consensus sequence, were identified. This sequence has undergone rapid evolution within the B. rapa genome and has diverged among the related species of Brassicaceae. A study of SSRs demonstrated a non-random distribution with a greater abundance within predicted intergenic regions. Our results provide an initial characterization of the genome of B. rapa and provide the basis for detailed analysis through whole-genome sequencing.


Gait Phase Subdivision and Leg Stiffness Estimation During Stair Climbing.
Leg stiffness is considered a prevalent parameter used in data analysis of leg locomotion during different gaits, such as walking, running, and hopping. Quantification of the change in support leg stiffness during stair ascent and descent will enhance our understanding of complex stair climbing gait dynamics. The purpose of this study is to investigate a methodology to estimate leg stiffness during stair climbing and subdivide the stair climbing gait cycle. Leg stiffness was determined as the ratio of changes in ground reaction force in the direction of the support leg Fl (leg force) to the respective changes in length Ll during the entire stance phase. Eight subjects ascended and descended an instrumented staircase at different cadences. In this study, the changes of leg force and length (force-length curve) are described as the leg stiffness curve, the slope of which represents the normalized stiffness during stair climbing. The stair ascent and descent gait cycles were subdivided based on the negative and positive work fluctuations of the center-of-mass (CoM) work rate curve and the characteristics of leg stiffness. We found that the leg stiffness curve consists of several segments in which the force-length relationship was similarly linear and the stiffness value was relatively constant; the phase divided by the leg stiffness curve corresponds to the phase divided by the CoM work rate curve. The results of this study may guide biomimetic control strategies for a wearable lower-extremity robot for the entire stance phase during stair climbing.


Actin cytoskeleton remodeling during early Drosophila furrow formation requires recycling endosomal components Nuclear-fallout and Rab11.
Cytokinesis requires a dramatic remodeling of the cortical cytoskeleton as well as membrane addition. The Drosophila pericentrosomal protein, Nuclear-fallout (Nuf), provides a link between these two processes. In nuf-derived embryos, actin remodeling and membrane recruitment during the initial stages of metaphase and cellular furrow formation are disrupted. Nuf is a homologue of arfophilin-2, an ADP ribosylation factor effector that binds Rab11 and influences recycling endosome (RE) organization. Here, we show that Nuf is an important component of the RE, and that these phenotypes are a consequence of Nuf activities at the RE. Nuf exhibits extensive colocalization with Rab11, a key RE component. GST pull-downs and the presence of a conserved Rab11-binding domain in Nuf demonstrate that Nuf and Rab11 physically associate. In addition, Nuf and Rab11 are mutually required for their localization to the RE. Embryos with reduced levels of Rab11 produce membrane recruitment and actin remodeling defects strikingly similar to nuf-derived embryos. These analyses support a common role for Nuf and Rab11 at the RE in membrane trafficking and actin remodeling during the initial stages of furrow formation.


The effectiveness of skills training for improving outcomes in supported employment.
This study evaluated whether a supplementary skills training program improved work outcomes for clients enrolled in supported employment programs. Thirty-five recently employed clients with severe mental illness who were receiving supported employment services at a free-standing agency were randomly assigned to participate in either the workplace fundamentals program, a skills training program designed to make work more "successful and satisfying," or treatment as usual. Knowledge of workplace fundamentals (for example, identifying workplace stressors, problem solving, and improving job performance) was assessed at baseline and at nine months; employment outcomes and use of additional vocational services were tracked for 18 months. Clients in the workplace fundamentals group (N=17) improved more in knowledge of workplace fundamentals than those in the control group (N=18) at the nine-month follow-up, but the two groups did not differ in the number of hours or days worked, salary earned, or receipt of additional vocational services over the 18-month period. In general, clients in this study had higher educational levels and better employment outcomes than clients in most previous studies of supported employment, making it difficult to detect possible effects of the skills training intervention on work. Supplementary skills training did not improve work outcomes for clients who were receiving supported employment.


Deciding for others.
Decision making for incompetent elderly people is an increasingly serious issue for American society. The decision-making processes we choose will reflect choices among a number of ethical principles--those specifying the purpose of substituted judgment, those guiding the surrogate decision maker, and those used in choosing the surrogate--and depends as well on the way we construe the concept of decision-making competence.


Schneiderian membrane thickness variation following endodontic procedures: a retrospective cone beam computed tomography study.
To assess the change of the Schneider membrane thickness measured by CBCT before and after root canal treatment, retreatment and pulp capping procedures. This retrospective study was conducted on CBCT scans of a patient population of Guy's Hospital NHS Foundation Trust, London. Three groups of patients were studied: Group 1 consisted of patients referred for primary endodontic treatment; Group 2 for endodontic retreatment; Group 3 for indirect pulp capping procedures (serving as a control group). Follow up scans were carried out 1 year after treatment. Measurements were carried out on CBCT scans and data were analysed statistically by Wilcoxon Signed Rank Test. Linear regression was used to assess predictive parameters for membrane thickness. A statistically significant reduction of the Schneider membrane thickness was observed one year after endodontic treatment and retreatment (P < 0.05) but no significant reduction was observed after pulp capping procedures. Linear regression showed that age and gender were significant predictors influencing the Schneider membrane thickness. Within the limitations of this retrospective study, following root canal treatment and re-treatment a Schneiderian membrane thickness reduction occurred at 1-year follow-up. The removal of odontogenic infection following endodontic treatment may help reducing the thickness of the Schneider membrane.


Multiple Facets of Cellular Homeostasis and Regeneration of the Mammalian Liver.
Liver regeneration occurs in response to diverse injuries and is capable of functionally reestablishing the lost parenchyma. This phenomenon has been known since antiquity, encapsulated in the Greek myth where Prometheus was to be punished by Zeus for sharing the gift of fire with humanity by having an eagle eat his liver daily, only to have the liver regrow back, thus ensuring eternal suffering and punishment. Today, this process is actively leveraged clinically during living donor liver transplantation whereby up to a two-thirds hepatectomy (resection or removal of part of the liver) on a donor is used for transplant to a recipient. The donor liver rapidly regenerates to recover the lost parenchymal mass to form a functional tissue. This astonishing regenerative process and unique capacity of the liver are examined in further detail in this review.


Uncomplicated acute myocardial infarction. Methods of nonlytic management.
Therapy for acute myocardial infarction has its most compelling effect when the patient is seen early in the course of illness. In this article, the authors discuss the status of nonlytic medications during the acute phase of Q-wave infarction and also examine the role of risk modification and stratification in long-term survival of the patient.


Resolution of anaemia in a cohort of HIV-infected patients with a high prevalence and incidence of tuberculosis receiving antiretroviral therapy in South Africa.
Anaemia is frequently associated with both HIV-infection and HIV-related tuberculosis (TB) in antiretroviral therapy (ART)-naïve patients in sub-Saharan Africa and is strongly associated with poor prognosis. However, the effect of ART on the resolution of anaemia in patient cohorts with a high prevalence and incidence of tuberculosis is incompletely defined and the impact of TB episodes on haemoglobin recovery has not previously been reported. We therefore examined these issues using data from a well-characterised cohort of patients initiating ART in South Africa. Prospectively collected clinical and haematological data were retrospectively analysed from patients receiving ART in a South African township ART service. TB diagnoses and time-updated haemoglobin concentrations, CD4 counts and HIV viral loads were recorded. Anaemia severity was classified according to WHO criteria. Multivariable logistic regression analysis was used to determine factors independently associated with anaemia after 12 months of ART. Of 1,140 patients with baseline haemoglobin levels, 814 were alive in care and had repeat values available after 12 months of ART. The majority of patients were female (73%), the median CD4 count was 104 cells/uL and 30.5% had a TB diagnosis in the first year of ART. At baseline, anaemia (any severity) was present in 574 (70.5%) patients and was moderate/severe in 346 (42.5%). After 12 months of ART, 218 (26.8%) patients had anaemia of any severity and just 67 (8.2%) patients had moderate/severe anaemia. Independent predictors of anaemia after 12 months of ART included greater severity of anaemia at baseline, time-updated erythrocyte microcytosis and receipt of an AZT-containing regimen. In contrast, prevalent and/or incident TB, gender and baseline and time-updated CD4 cell count and viral load measurements were not independent predictors. Although anaemia was very common among ART-naive patients, the anaemia resolved during the first year of ART in a large majority of patients regardless of TB status without routine use of additional interventions. However, approximately one-quarter of patients remained anaemic after one year of ART and may require additional investigations and/or interventions.


Acute cerebellar ataxia and peripheral neuropathy due to an atypical infection.
This 18-year-old boy presented to the hospital with symptoms of cerebellar dysfunction preceded by an acute febrile illness with rash. Examination showed evidence of left-sided cerebellar dysfunction and polyneuropathy. Empirical treatment for leptospirosis and scrub typhus was initiated. MRI was normal. Other organ dysfunctions in the form of thrombocytopenia and transaminitis were also observed. He recovered without sequelae. A diagnosis of acute cerebellar ataxia and polyneuropathy due to scrub typhus was made.


A case of delayed inflammatory filler reaction following vaccination with succesful response to colchicine.
Delayed inflammatory reactions (DIRs) associated with hyaluronic acid injections are not rare and can be seen in up to 4.25% of patients. Although the exact mechanism is not clear, several triggering factors, including infections, trauma, and dental procedures, were reported in the literature. A 43-year-old female patient treated with HA fillers developed an inflammatory reaction following vaccination in all areas of injection, including temples, lips, and lower eyelids. Systemic steroid and ciprofloxacin were used as a first-line treatment without response. Colchicine 1 mg/day along with hyaluronidase in lower eyelids improved all lesions successfully.


Infleuence of a neonatal spleen transplant on hematopoiesis of hereditarily asplenic mice.
Hereditarily asplenic mice and normal litternates were transplanted subcatneously with 20x10(6) congenic spleen cells at birth. Eighty per cent of the recipients developed subcutaneous nodules closely resembling the spleen structure seen ia a normal mouse. The growth of the graft was associated with hyperplasis of the majority of the bone marrow cellseries and an increased number of stem cells (CFU-spleen) and agar colony forming cells (CFC) per femoral shaft. Particularly noticeable was the hyperplasia of the granulocytic series which paralleled the increase of CFC number and of serum colony stimulating factor. The presence of the graft did not modify the erthrocytic seroes and the leukocytics of asplenic mice but reduced the average platelet count. It is xonxluded that the growth of the transplant was associated with the hematopoietic alteration described. These results would also indicate humoral or cellular influences of the spleen on the release of or production of marrow cells.


Thigh compression.
The aim of this overview is to discuss the role of thigh compression for the management of venous and lymphatic diseases. The most important indications for thigh compression are prevention and treatment of sequelae of superficial vein procedures (surgery or endovenous procedures), prevention and therapy of deep vein thrombosis (DVT), post-thrombotic syndrome and lymphoedema. The intended effects depend mainly on narrowing/occlusion of deep and superficial veins on which the body position and the applied pressure play a crucial role. While in the horizontal position thigh veins can be narrowed by the light pressure of a thromboprophylactic stocking, much higher pressure is needed to compress thigh veins effectively during standing and walking. This is shown by magnetic resonance imaging (MRI) performed in the supine and upright position. Using pads, rolls or specially designed devices, the local pressure under conventional compression garments or bandages over a treated vein can be increased considerably. In patients with deep valve incompetence, beneficial haemodynamic effects of strong thigh compression have been demonstrated, but clinical studies in this field are still lacking. Thigh compression reduces oedema in patients with DVT and lymphoedema.


Differential changes in islet lysosomal enzyme activities in aging obese hyperglycemic mice.
The pattern of pancreatic islet lysosomal enzyme activities was investigated in adult obese mice (aged 5-7 months), old obese mice (aged 9-17 months) and aged-matched old "obese" mice suffering from excessive weight loss. A series of lean NMRI mice of comparable age was included as controls. It was observed that the islet activity of the glucose producing glycogenolytic hydrolase, acid amyloglucosidase, was excessively high in the adult obese mouse, being about 10 times higher than in the adult lean mouse. This high activity was reduced by about 65% in the islets of old obese mice and by about 80% in old mice suffering from weight loss. When glycogen and maltose were compared as substrates for the alpha-1,4-glucoside splitting activity, the ratio, glycogen splitting/maltose splitting activity in adult obese mice (1.68) showed amyloglucosidase predominance, whereas the ratio in old obese mice (0.67), and in old mice suffering from weight loss (0.79) revealed a significant change in this relation. The extremely elevated plasma insulin levels in the adult obese mice were reduced by about 65% in old obese mice and by about 95% in old mice with excessive weight loss and thus displaying the same pattern as islet amyloglucosidase activity. Further, in normoglycemic obese mice a highly significant correlation (r = 0.85; p less than 0.001) was found between islet acid amyloglucosidase activity and the actual insulin secretory rate as reflected by the plasma insulin concentrations. The activity of islet N-acetyl-beta-D-glucosaminidase showed an activity pattern opposite to that of acid amyloglucosidase.(ABSTRACT TRUNCATED AT 250 WORDS)


Development and validation of RP-HPLC method for simultaneous estimation of glimepiride and sildenafil citrate in rat plasma-application to pharmacokinetic studies.
A simple and sensitive method was developed for simultaneous estimation of Glimepiride (GLIM) and Sildenafil citrate (SIL) in rat Plasma by reverse phase high performance liquid chromatography (RP-HPLC). The drug samples were extracted by liquid-liquid extraction with 300 µl of acetonitrile and 5 ml of diethyl ether. Chromatographic separation was achieved on C18 column using methanol: water (85:15 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection at 230 nm. The retention time of GLIM and SIL was found to be 2.5 and 4.0 min respectively with total run time of 7 min. The developed method was validated for accuracy, precision, linearity and recovery. The method was linear and found to be acceptable over the range of 100-12 000 ng/ml. The method was successfully applied for the analysis of rat plasma sample for application to pharmacokinetic.


Effect of novel bicaval anastomosis technique for transplantation with and without prior cardiac surgery history.
To evaluate the graft outcomes after orthotopic heart transplantation (HTx) with a novel bicaval anastomosis technique between recipients with and without a history of prior cardiac surgery. Of 70 patients who underwent HTx with a novel four-corners traction bicaval anastomosis technique from August 2017 to November 2019, 60 recipients underwent the HTx procedure as their first cardiac surgery (group A), while 10 recipients underwent HTx after prior cardiac surgery (group B). Patients in the two groups were compared in terms of their preoperative baseline variables such as etiological categories, history of blood transfusion and panel reactive antibody (PRA), intraoperative operation time and blood infusion volume, postoperative treatment time, and complications such as acute rejection and 30-day mortality as well as survival rates. Preoperative variables were comparable in group A and group B except for the history of blood transfusion (0% vs. 90.0%, P<0.001, respectively); the level of PRA was 7.5%±5.8% and 9.5%±10.9% for group A and B, respectively (P=0.583), but the time of the operation was nearly 1 hour longer for group B than group A (all P<0.05). No cases of left atrial thrombosis and donor heart distortion were observed in either group. Reoperation (1.7% vs. 10.0%, P=0.267), infection (0% vs. 10.0%, P=0.142), other postoperative complications as well as the 30-day mortality (1.7% vs. 10.0%, P=0.267), and postoperative survival rates (91.5% vs. 90.0%, P=0.805) were comparable between the two groups (all P>0.05). Four-corner traction bicaval anastomosis combined with a continuous everting suture technique may result in approximately comparable prognoses for heart recipients with a history of cardiac surgery when compared with those without a history of cardiac surgery and this technique may reduce the incidence of left atrial thrombosis and distortion. Further follow-up of the long-term outcomes will be required to validate these results.


Maintenance of patency of central venous access devices by registered nurses in an acute ambulatory setting: an evidence utilisation project.
The aim of the project was to implement the best practice for the maintenance of patency for central venous access devices by registered nurses in an acute ambulatory setting. This project utilised the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice programs to facilitate a process of change using an audit, feedback and re-audit cycle as a strategy to improve clinical practice. The team conducted the project in three phases over a 5-month period (July to November 2011). It involved a sample size of 29 registered nurses. The compliance rate for both criteria increased post-implementation, demonstrating a positive improvement in compliance to the best practice. The pulsated flushing technique improved from 25% (baseline) to 93% (post-implementation) compliance rate. This showed a statistically significant improvement of 68% (χ(2) = 29.375, P = 0.000). The second criterion, the use of sterile normal saline to flush and lock the catheter, improved from 68% compliance in the baseline audit to 100% compliance rate in the post-implementation audit (χ(2) = 14.215, P = 0.005). This project utilised the process of audit, feedback and re-audit cycle as a strategy to improve clinical practice. It demonstrated the feasibility of translating evidence-based practice into the clinical setting, with remarkable improvement in maintaining patency of central venous access devices for patient with cancer. Finally, it is evidenced that the commitment and enthusiasm of team members and all the registered nurses in maintaining the patency of central venous access devices were the crucial factors for the success of this project. The support and assistance provided by the stakeholders also played an important role in the sustainment of the project.


Fibrinogen binds IgG antibody and enhances IgG-mediated phagocytosis.
While Fibrinogen (Fg) and Immunoglobulin G (IgG) are traditionally thought to have separate functions in thrombosis and immune response, recent studies suggest overlapping functions. Here we present evidence that Fibrinogen binds to IgG specifically, and that Fibrinogen-IgG interactions enhance phagocytosis. We demonstrate specific, saturable binding of Fibrinogen to immobilized IgG and its fragments on nitrocellulose or poly-(L)-Lys styrene plates using Biotin/Streptavidin-Horse Radish Peroxidase detection systems. We also demonstrated that GFP-expressing E.coli coated with anti-E.coli antibody (IgG) and Fibrinogen elicit higher rates of phagocytosis than either Fibrinogen or IgG-treated E.coli alone (p < 0.001). We conclude that Fibrinogen enhances phagocytosis and possibly other leukocyte functions in concert with IgGs. This mechanism might focus leukocyte action triggered by fibrinogen towards specific antigens.


Urbanization is a main driver for the larval ecology of Aedes mosquitoes in arbovirus-endemic settings in south-eastern Côte d'Ivoire.
Failure in detecting naturally occurring breeding sites of Aedes mosquitoes can bias the conclusions drawn from field studies, and hence, negatively affect intervention outcomes. We characterized the habitats of immature Aedes mosquitoes and explored species dynamics along a rural-to-urban gradient in a West Africa setting where yellow fever and dengue co-exist. Between January 2013 and October 2014, we collected immature Aedes mosquitoes in water containers in rural, suburban, and urban areas of south-eastern Côte d'Ivoire, using standardized sampling procedures. Immature mosquitoes were reared in the laboratory and adult specimens identified at species level. We collected 6,159, 14,347, and 22,974 Aedes mosquitoes belonging to 17, 8, and 3 different species in rural, suburban, and urban environments, respectively. Ae. aegypti was the predominant species throughout, with a particularly high abundance in urban areas (99.374%). Eleven Aedes larval species not previously sampled in similar settings of Côte d'Ivoire were identified: Ae. albopictus, Ae. angustus, Ae. apicoargenteus, Ae. argenteopunctatus, Ae. haworthi, Ae. lilii, Ae. longipalpis, Ae. opok, Ae. palpalis, Ae. stokesi, and Ae. unilineatus. Aedes breeding site positivity was associated with study area, container type, shade, detritus, water turbidity, geographic location, season, and the presence of predators. We found proportionally more positive breeding sites in urban (2,136/3,374, 63.3%), compared to suburban (1,428/3,069, 46.5%) and rural areas (738/2,423, 30.5%). In the urban setting, the predominant breeding sites were industrial containers (e.g., tires and discarded containers). In suburban areas, containers made of traditional materials (e.g., clay pots) were most frequently encountered. In rural areas, natural containers (e.g., tree holes and bamboos) were common and represented 22.1% (163/738) of all Aedes-positive containers, hosting 18.7% of the Aedes fauna. The predatory mosquito species Culex tigripes was commonly sampled, while Toxorhynchites and Eretmapodites were mostly collected in rural areas. In Côte d'Ivoire, urbanization is associated with high abundance of Aedes larvae and a predominance of artificial containers as breeding sites, mostly colonized by Ae. aegypti in urban areas. Natural containers are still common in rural areas harboring several Aedes species and, therefore, limiting the impact of systematic removal of discarded containers on the control of arbovirus diseases.


Evaluation of multiple regimens in leprosy.
Assessment of bacteraemia has been made at weekly intervals in 36 lepromatous leprosy patients who were put on different antileprosy drug under four regimens, viz., DDS alone, DDS in combination with rifampicin (DDS + RIF), clofazimine (DDS + CLF) and thiacetazone (DDS + TCT). In general, with the continuation of treatment the bacillary load in the blood decreased considerably while bacteriological index (BI) of the skin remained constant during the study. No significant difference was noted in M. leprae clearance from blood between the groups treated with DDS alone and groups treated in combination with CLF and TCT. However, DDS + RIF treatment was most efficient in clearing acid-fast bacilli (AFB) from blood as compared to those noted with other drug regimens.


Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.
Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system. To test the attenuation of the ketamine-induced BOLD signal by pretreatment with either a metabotropic glutamate receptor (mGluR) 2/3 or a mGluR2 agonist in healthy volunteers METHODS: We used a ketamine challenge pharmacological magnetic resonance imaging (phMRI) paradigm to assess the modulatory effects of single acute doses of LY2140023 (pomaglumetad methionil), the methionine prodrug of the mGluR2/3 agonist LY404039 (10, 40, and 160 mg; N = 16 subjects) and of LY2979165, and the alanine prodrug of the selective orthosteric mGluR2 agonist 2812223 (20 and 60 mg; N = 16 subjects). A reduction in the ketamine-evoked BOLD phMRI signal relative to placebo was observed at the highest doses tested of both LY2140023 and LY2979165. A relationship was observed between reduction of the BOLD signal and increasing plasma levels of 2812223 in the LY2979165 cohort. These results identify pharmacologically active doses of the group II mGluR agonist prodrugs LY2140023 and LY2979165 in humans. They also extend the classes of compounds that have been experimentally shown to reverse the ketamine-evoked phMRI signal in humans, further supporting the use of this method as a neuroimaging biomarker for assessing functional effects.


Management of peripheral nerve sheath tumors: 17 years of experience at Toronto Western Hospital.
OBJECTIVE A surgical series of 201 benign and malignant peripheral nerve sheath tumors (PNSTs) was assessed to characterize the anatomical and clinical presentation of tumors and identify predictors of neurological outcome, recurrence, and extent of resection. METHODS All surgically treated PNSTs from the Division of Neurosurgery at Toronto Western Hospital from 1993 to 2010 were reviewed retrospectively. Data were collected on patient demographics, clinical presentation, surgical technique, extent of resection, postoperative neurological outcomes, and recurrence. RESULTS One hundred seventy-five patients with 201 tumors had adequate follow-up for analysis. There were 182 benign and 19 malignant PNSTs. Of the benign lesions, 133 were schwannomas, 21 of which were associated with a diagnosis of schwannomatosis. There were 49 neurofibromas, and 26 were associated with neurofibromatosis Type 1 (NF1). Patients presenting with schwannomas were significantly older than those with neurofibromas. Schwannomas were more readily resected than neurofibromas, with the extent of resection of the former influenced by tumor location. Patients with benign PNSTs typically presented with a painful mass and less frequently with motor deficits. The likelihood of worsened postoperative motor function was decreased in patients with fully resected tumors or preoperative deficits. Recurrence of schwannomas and neurofibromas were seen more frequently in patients diagnosed with NF3 and NF1, respectively. Subtotal resection was associated with the increased recurrence of all benign lesions. CONCLUSIONS Outcomes following resection of benign PNSTs depend on tumor histopathology, tumor location, and genetic predisposition syndrome. Gross-total resection should be attempted for benign lesions where possible. The management of malignant PNSTs remains challenging, requiring a multimodal approach.


Specific inhibition of long-lasting, L-type calcium channels by synthetic parathyroid hormone.
The effect of an active synthetic N-terminal fragment of bovine parathyroid hormone (bPTH), bPTH-(1-34), on Ca2+ channels was studied in mouse neuroblastoma cells (N1E-115). With the whole-cell variation of the patch-clamp technique, T (transient) and L (long-lasting) types of Ca2+ currents were identified. Pharmacological characterization showed that the L current was amplified by the Ca2+ channel stimulator BAY K-8644, but the T current was unaffected. The administration of bPTH-(1-34) produced dose-related inhibition of the L current, which could be reversed by BAY K-8644. The peptide had no effect on the T current. In addition, use of the fluorescent indicator fura-2 showed that bPTH-(1-34) inhibited the KCl-stimulated increase in intracellular free Ca2+ in neuroblastoma cells with L channels but not in cells with T channels. An inactivated (oxidized) preparation of bPTH-(1-34) failed to affect the L current. High-affinity binding of labeled PTH analog to these neuroblastoma cells was also demonstrated. In addition, bPTH-(1-34) inhibited the L current in cultured vascular smooth muscle cells from rat tail artery. These data indicate that, in some tissues, PTH can act as an endogenous blocker of Ca2+ entry.


The impact of undiagnosed primary biliary cholangitis.
Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by symptoms with a major impact on the quality of life. The aim of this study was to identify patients with undiagnosed PBC who are not under hepatology follow-up and to assess the clinical impact of lack of adequate treatment and surveillance. Adult patients with a positive antimitochondrial antibodies (AMA) titer were identified from local biochemistry records. Patients with probable PBC who were not known by the hepatology services were invited to accurately stage their disease and optimize medical management. A total of 214 AMA-positive patients were identified, 148 of whom had diagnostic criteria for PBC. Twenty-three patients were not known by the hepatology services, most of them followed by specialties other than gastroenterology. These patients had significantly higher liver stiffness compared to those followed by the hepatology services (14.3 kPa vs. 6.2 kPa; P = 0.009). A large percentage of untreated individuals reported fatigue (72.7%) and pruritus (27.3%). A substantial number of patients with PBC are not known to have hepatology services with a significant long-term impact from a lack of follow-up and therapy. Strategies must be established to identify these patients and reduce the disease's progressive nature.


Handle with care: Assessing performance measures of medical AI for shared clinical decision-making.
In this article I consider two pertinent questions that practitioners must consider when they deploy an algorithmic system as support in clinical shared decision-making. The first question concerns how to interpret and assess the significance of different performance measures for clinical decision-making. The second question concerns the professional obligations that practitioners have to communicate information about the quality of an algorithm's output to patients in light of the principles of autonomy, beneficence, and justice. In the article I review the four standard performance measures used to evaluate and validate algorithms, outline their role in the discussion of algorithmic fairness, and discuss the professional responsibilities that practitioners face when communicating information about these measures to patients.


Functional connectivity patterns of medial and lateral macaque frontal eye fields reveal distinct visuomotor networks.
It has been previously shown that small- and large-amplitude saccades have different functions during vision in natural environments. Large saccades are associated with reaching movements toward objects, whereas small saccades facilitate the identification of more detailed object features necessary for successful grasping and manual manipulation. To determine whether these represent dichotomous processing streams, we used resting-state functional MRI to examine the functional connectivity patterns of the medial and lateral frontal eye field (FEF) regions that encode large- and small-amplitude saccades, respectively. We found that the spontaneous blood oxygen level-dependent signals of the medial FEF were functionally correlated with areas known to be involved in reaching movements and executive control processes, whereas lateral FEF was functionally correlated with cortical areas involved in object processing and in grasping, fixation, and manipulation of objects. The results provide strong evidence for two distinct visuomotor network systems in the primate brain that likely reflect the alternating phases of vision for action in natural environments.


Enhanced patient reported outcome measurement suitable for head and neck cancer follow-up clinics.
The 'Worse-Stable-Better' (W-S-B) question was introduced to capture patient-perceived change in University of Washington Quality of Life (UW-QOL) domains. 202 head and neck cancer patients in remission prospectively completed UW-QOL and Patients Concerns Inventory (PCI). For each UW-QOL domain, patients indicated whether over the last month things had worsened (W), remained stable (S) or were better (B). 202 patients at 448 attendances selected 1752 PCI items they wanted to discuss in consultation, and 58% (1024/1752) of these were not covered by the UW-QOL. UW-QOL algorithms highlighted another 440 significant problems that the patient did not want to discuss (i.e. the corresponding items on the PCI were not selected).After making allowance for UW-QOL algorithms to identify 'significant problems' and PCI selection of corresponding issues for discussion there remained clear residual and notable variation in W-S-B responses, in particular to identify patients with significant problems that were getting worse, and patients without significant problems that wanted to discuss issues that were getting worse. Changes in mean UW-QOL scores were notably lower for those getting worse on the W-S-B question, typically by 10 or more units a magnitude that suggests clinically important changes in score. The W-S-B question adds little questionnaire burden and could help to better identify patients who might benefit from intervention. The results of this study suggest that the UW-QOL with the W-S-B modification should be used together with the PCI to allow optimal identification of issues for patient-clinician discussion during routine outpatient clinics.


Chemical composition of the cell walls of Bacillus stearothermophilus.
Cell walls were isolated by mechanical disruption of mid-log phase cells of Bacillus stearothermophilus NCA 1503-4R grown in Trypticase-yeast extract-fructose medium at 55 C. The cell walls were purified by treatment with sodium dodecyl sulfate (SDS) and incubation with deoxyribonuclease and trypsin. The cell wall peptidoglycan contained glucosamine, muramic acid, alpha, epsilon-diaminopimelic acid, and glutamic acid. Low amounts of glycine, galactosamine, serine, aspartic acid, lysine, and valine were also present. The relative mole ratios of glutamic acid-alpha, epsilon-diaminopimelic acid-glycine-alanine were 1.00:1.26:0.08:1.55. The cell walls were free from ribonucleic acid and deoxyribonucleic acid and contained less than 0.2% chloroform-methanol extractable lipid and 0.09 mumole of phosphorus per mg of cell wall. Teichoic acid was not detected in the cell walls of this organism. Cell walls isolated without treatment with SDS contained 7.5% chloroform-methanol extractable lipid, 0.24 mumole of phosphorus per mg of cell wall, and relatively high concentrations of all amino acids. These results suggest that the extracted lipid is not a cell wall component per se, but a contaminant from the lipoprotein cell membrane.


Are minority status children's cross-ethnic friendships beneficial in a multiethnic context?
Past research has demonstrated the negative impact of perceived ethnic discrimination (PED) on psychological well-being among children. Given research demonstrating the benefits of cross-ethnic friendship for children's intergroup attitudes, we examined whether cross-ethnic friendships would attenuate the effects of PED on well-being and resilience within a multi-ethnic context. Two hundred and forty-seven South Asian British children (M = 11 years) recruited from 37 classrooms completed measures of perceived cross-ethnic friendship quantity and quality, PED, psychological well-being, and resilience. Friendship quality, but not quantity, had direct positive associations with psychological well-being and resilience. A higher quantity of cross-ethnic friendships moderated the negative effects of PED on both outcomes. Results suggest that cross-ethnic friendships are beneficial for South Asian British children by functioning as a protective factor from the negative effects of discrimination within a multi-ethnic context.


Gangliosides in neuroblastomas.
Neuroblastomas from children presenting with tumors at various ages and different primary sites (abdominal, adrenals, pelvic, and thoracic) were studied. Analysis of the ganglioside patterns of 53 tumors indicated that patients who were either disease positive 2 yr following surgery or dead of disease, had significantly (p less than 0.005) less GT1b plus GD1b than tumors from patients that were disease free 2 yr post surgery. The presence of GD2 in 45 of the tumors correlates well with the suggestion that it can be used as a marker in neuroblastoma diagnosis. Children with thoracic neuroblastomas have a significantly better prognosis than children with tumors in other anatomic sites. Analysis of the ganglioside composition of these tumors only, indicated that they had a significantly higher (p less than 0.005) concentration of GT1b and GD1b and a significantly lower concentration (p less than 0.025) of monosialogangliosides than those patients who were dead of disease or had persistent disease. These results suggest that low levels of GT1b and GD1b correlate with a poor prognosis. The thoracic neuroblastomas may be comprised of more "differentiated" neuroblastoma cells (ganglioside patterns more similar to the CNS), and this may contribute to the fact that about 85% of children with thoracic neuroblastoma recover. To understand why the ganglioside pattern may serve as a prognostic indicator for neuroblastoma, it is necessary to know whether gangliosides have specific roles in neuronal differentiation. Our approach to this question is to compare the effect(s) of added ganglioside or the corresponding oligosaccharide on neuroblastoma cells. Results obtained suggest that the oligosaccharide from GM1 is able to enhance neuritogenesis by S20Y murine neuroblastoma cells to the same extent that GM1 does.


Validated LC-MS/MS method for the determination of mirodenafil in rat plasma and its application to a comparative pharmacokinetic study of the free base and hydrochloride salt forms of mirodenafil.
In this study, the pharmacokinetics of 2 forms of mirodenafil, namely the base form and the hydrochloride salt form, were investigated in rats. The 2 forms were orally administered to rats and the plasma concentrations of mirodenafil were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mirodenafil base and hydrochloride salt forms showed similar pharmacokinetic profiles in terms of their maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC). The time to peak concentration (Tmax) of the base form was slightly greater than that of the salt form, but this difference was not statistically significant. These results suggest that the mirodenafil base and hydrochloride forms are pharmacokinetically equivalent in rats, and thus the base form could be used in various mirodenafil formulations as a substitute for the existing mirodenafil hydrochloride form.


The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer.
The effect of anti-programmed cell death 1 (PD-1) antibody in Epstein-Barr virus-associated gastric cancer (EBVaGC) was debatable, and no predictive biomarkers for efficacy have been reported. Public reports on anti-PD-1 antibody monotherapy-treated EBVaGC with available programmed death ligand-1 (PD-L1) expression status were summarized and analyzed. Relevance with clinicopathologic characteristics of PD-L1 expression by immunohistochemistry was analyzed in 159 patients diagnosed with EBVaGC. Relevance with genomic transcriptome and mutation profile of PD-L1 status in EBVaGC was assessed with three datasets, the cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) GSE51575, and GSE62254. Based on the data from 8 reports, patients with positive PD-L1 expression (n = 30) had significantly superior objective response rate (ORR) than patients with negative PD-L1 expression (n = 9) (63.3% vs. 0%, P = .001) in EBVaGC receiving anti-PD-1 antibody monotherapy. PD-L1 positivity was associated with less aggressive clinicopathological characteristics and was an independent predictor for a longer disease-free survival (hazard ratio [HR] and 95% CI: 0.45 [0.22-0.92], P = .03) and overall survival (HR and 95% CI: 0.17 [0.06-0.43], P < .001). Analysis of public EBVaGC transcriptome and mutation datasets revealed enhanced immune-related signal pathways in PD-L1high EBVaGC and distinct mutation patterns in PD-L1low EBVaGC. PD-L1 positivity indicates a subtype of EBVaGC with 'hot' immune microenvironment, lower aggressiveness, better prognosis, and higher sensitivity to anti-PD-1 immunotherapy.


Enhanced planar perovskite solar cell efficiency and stability using a perovskite/PCBM heterojunction formed in one step.
Perovskite/PCBM heterojunctions are efficient for fabricating perovskite solar cells with high performance and long-term stability. In this study, an efficient perovskite/PCBM heterojunction was formed via conventional sequential deposition and one-step formation processes. Compared with conventional deposition, the one-step process was more facile, and produced a perovskite thin film of substantially improved quality due to fullerene passivation. Moreover, the resulting perovskite/PCBM heterojunction exhibited more efficient carrier transfer and extraction, and reduced carrier recombination. The perovskite solar cell device based on one-step perovskite/PCBM heterojunction formation exhibited a higher maximum PCE of 17.8% compared with that from the conventional method (13.7%). The device also showed exceptional stability, retaining 83% of initial PCE after 60 days of storage under ambient conditions.


Using ivermectin-treatment coverage among schoolchildren monitored by schoolteachers as a proxy of population coverage in areas of Uganda where onchocerciasis is endemic.
In the control of onchocerciasis using mass treatment with ivermectin, coverage needs to be monitored regularly so that communities with poor or insufficient coverage can be identified and timely and appropriate interventions then instituted. The aim of the present study was to assess whether ivermectin-treatment coverage in schoolchildren, as monitored by schoolteachers, could be used as a proxy of population coverage. Although the coverages estimated in schoolchildren were found to be significantly correlated with estimates based on household surveys (P=0.01), there was poor correlation between either school and household-survey coverage and the values recorded in community registers. Although the community-register figures are the ones which the district health services normally use to report treatment coverage, they may be unreliable. Ivermectin-treatment coverage in schoolchildren monitored by schoolteachers could give a good and more accurate approximation of total population coverage. Further, large-scale studies, that take into consideration the cost-effectiveness of the various methods available to validate reported treatment coverage, are recommended.


[Post infection antiidiotype vaccination against HIV: results of a phase Ia pilot study].
The mAb IOT4A against the HIV-gp 120 binding site on CD4 was shown to elicit the production of specific anti-idiotypes in rabbits neutralising HIV-1 in vitro. This study was designed in order to determine the safety and efficacy of the mAb IOT4A for the immunization of HIV+ volunteers. 10 patients in stages WR2-WR4B of HIV-disease were given six s.c. injections of the mAb IOT4A as an alum precipitate (each 3 patients receiving 0.6 or 1.2 mg, 4 patients receiving 2.4 mg). 6 patients subsequently received a booster immunization with the same dose of the mAb IOT4A. The immunization schedule was accompanied by monitoring clinical, immunologic and virologic parameters. No systemic toxic or allergic effects of the idiotype vaccine were observed. 8/10 vaccinees displayed a delayed-type hypersensitivity at the location of antibody administration beyond the third injection. The relative and absolute CD4 count showed a sustained increase in 8/10 patients at the end of the booster immunization and an additional raise after booster immunization in 6/6 patients. 624 antigen levels became negative in 2/2 patients during vaccination. In 4/10 patients in increase in HIV/gp 120 antigen binding titres was observed. HIV neutralisation titer remained stable throughout the observation period, and no progression in HIV disease was observed in all patients included in this study. The administration of the mAb IOT4A as a vaccine in HIV-infected volunteers was well tolerated. The mAb ITO4A induced the production of specific anti-idiotypes, that might have been of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of potential biomarkers and pathways in ulcerative colitis with combined public mRNA and miRNA expression microarray data analysis.
Ulcerative colitis (UC) is a chronic, relapsing and non-specific inflammatory disease, involving various genes and pathways in their pathogenesis. Increasing evidences have showed that microRNAs (miRNAs) act as key post-transcriptional regulators of gene expression in UC. This current study aimed to identify key miRNAs, potential target genes, and relevant pathways involved in UC to uncover their underlying molecular mechanisms by using bioinformatics analysis. The mRNA and miRNA expression profiles were retrieved and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and miRNAs (DEMIs) were obtained by using the R software package. A total of 79 DEGs and 47 DEMIs were obtained. And a panel of miRNAs and their target mRNAs were identified. It showed that miR-1231 may be a key regulator for DUOX2 and TFF1. CCL11 may be potentially targeted by miR-625. MMP1 may play vital roles in the development of UC by regulating the miR-1228/PPAR signaling pathway. In addition, we validated the most significantly up/down-expressed miRNAs (miR-92b, miR-625) and two of their corresponding target mRNAs (AQP8 and TAGAP, CCL11 and CHI3L1) in colon tissues of UC models preliminarily. The results were consistent with the microarray analysis. These findings may provide new insights into representing key mechanisms associated with the development of UC.


Changes in pulsatile release of neuropeptide-Y and luteinizing hormone (LH)-releasing hormone during the progesterone-induced LH surge in rhesus monkeys.
In previous studies we have shown that the pulsatility of LH-releasing hormone (LHRH) release in gonadectomized monkeys is modulated by input from neuropeptide-Y (NPY) neurons: 1) the endogenous release of NPY in the stalk-median eminence (S-ME) was pulsatile; 2) NPY pulses were temporally correlated with LHRH pulses, with NPY pulses preceding LHRH pulses by approximately 5 min; and 3) infusion of NPY into the S-ME stimulated LHRH release, whereas 4) infusion of antiserum to NPY suppressed endogenous LHRH pulses. It is not known, however, whether ovarian steroid hormones alter the pulsatility of NPY and LHRH release or whether the temporal correlation of NPY and LHRH pulses is maintained during the LH surge. In the present study we examined the changes in pulsatile release of NPY and LHRH in ovariectomized monkeys treated with estradiol benzoate (EB) followed by progesterone or oil. Using push-pull perfusion, perfusate samples from S-ME were collected at 10-min intervals for 15 h. NPY and LHRH concentrations in the perfusates were measured by RIA. Circulating LH levels were also monitored by periodic blood sampling and RIA. Injection of progesterone (sc) after EB induced an LH surge with a peak latency of 7.3 +/- 1.3 h (mean +/- SE) in seven of seven monkeys, whereas oil injection after EB elicited an LH surge in none of seven monkeys. The progesterone-induced LH surge was associated with an increase in LHRH release; the mean, pulse amplitude, and pulse frequency increased significantly (for all, P < 0.05) 4-8 h after progesterone. NPY pulse frequency also increased significantly (P < 0.05) 4-8 h after progesterone treatment, whereas mean release and pulse amplitude did not change in response to progesterone. Oil treatment after EB administration did not alter any parameter of LHRH and NPY pulses. Interestingly, the NPY and LHRH pulses were highly correlated (P < 0.001) in monkeys treated with either EB-progesterone or EB-oil, and NPY pulses preceded LHRH pulses by 4.8 +/- 0.7 and 5.1 +/- 0.6 min, respectively. In summary, 1) an episode of increased LHRH release occurs before and during the progesterone-induced LH surge; 2) acceleration of LHRH pulse frequency and the increase in LHRH pulse amplitude after progesterone are accompanied by acceleration of NPY pulse frequency; and 3) ovarian steroids do not affect the temporal correlation between NPY and LHRH pulses.(ABSTRACT TRUNCATED AT 400 WORDS)


Gluconeogenesis is associated with high rates of tricarboxylic acid and pyruvate cycling in fasting northern elephant seals.
Animals that endure prolonged periods of food deprivation preserve vital organ function by sparing protein from catabolism. Much of this protein sparing is achieved by reducing metabolic rate and suppressing gluconeogenesis while fasting. Northern elephant seals (Mirounga angustirostris) endure prolonged fasts of up to 3 mo at multiple life stages. During these fasts, elephant seals maintain high levels of activity and energy expenditure associated with breeding, reproduction, lactation, and development while maintaining rates of glucose production typical of a postabsorptive mammal. Therefore, we investigated how fasting elephant seals meet the requirements of glucose-dependent tissues while suppressing protein catabolism by measuring the contribution of glycogenolysis, glycerol, and phosphoenolpyruvate (PEP) to endogenous glucose production (EGP) during their natural 2-mo postweaning fast. Additionally, pathway flux rates associated with the tricarboxylic acid (TCA) cycle were measured specifically, flux through phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate cycling. The rate of glucose production decreased during the fast (F(1,13) = 5.7, P = 0.04) but remained similar to that of postabsorptive mammals. The fractional contributions of glycogen, glycerol, and PEP did not change with fasting; PEP was the primary gluconeogenic precursor and accounted for ∼95% of EGP. This large contribution of PEP to glucose production occurred without substantial protein loss. Fluxes through the TCA cycle, PEPCK, and pyruvate cycling were higher than reported in other species and were the most energetically costly component of hepatic carbohydrate metabolism. The active pyruvate recycling fluxes detected in elephant seals may serve to rectify gluconeogeneic PEP production during restricted anaplerotic inflow in these fasting-adapted animals.


Efficient transformation of phytopathogenic strains of Xanthomonas species.
Efficient transformation and conjugation systems for use in phytopathogenic strains of Xanthomonas species were developed with a dual-function plasmid vector, pBXC12, which was constructed from a newly isolated Xanthomonas citri plasmid, pXCL6, and pBR328. By using this system, pBR328 could also transform the same strains of Xanthomonas. The systems make useful cloning vectors for the study of genes involved in the plant pathogenesis of this species.


Rapid Aqueous Photouncaging by Red Light.
This work describes three new red-photocleavable dyes. The best-performing dye exhibits a quantum yield of 5.7% in 30:70 v/v water/acetonitrile and approximately 80% release of benzoic acid using a 626 nm LED. Photo-orthogonality between this dye and a UV-activated photouncaging group was demonstrated. Additionally, a qualitative comparison between the same pair of dyes in a gel was performed, highlighting the superior penetration depth that can be achieved using the newly reported dye.


Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by Nab4/Hrp1 in vivo.
The Saccharomyces cerevisiae RNA-binding protein Nab4/Hrp1 is a component of the cleavage factor complex required for 3' pre-mRNA processing. Although the precise role of Nab4/Hrp1 remains unclear, it has been implicated in correct positioning of the cleavage site in vitro. Here, we show that mutation or overexpression of NAB4/HRP1 alters polyA cleavage site selection in vivo. Using bioinformatic analysis, we identified four related motifs that are statistically enriched in Nab4-associated transcripts; each motif is similar to the known binding site for Nab4/Hrp1. Site-directed mutations in predicted Nab4/Hrp1 binding elements result in decreased use of adjacent cleavage sites. Additionally, we show that the nab4-7 mutant displays a striking resistance to toxicity from excess copper. We identify a novel target of alternative 3' pre-mRNA processing, CTR2, and demonstrate that CTR2 is required for the copper resistance phenotype in the nab4-7 strain. We propose that alternative 3' pre-mRNA processing is mediated by a Nab4-based mechanism and that these alternative processing events could help control gene expression as part of a physiological response in S. cerevisiae.


Side chain to side chain cyclization of an enkephalin analog results in loss of opioid receptor selectivity.
The cyclic enkephalin analog H-Tyr-D-Lys-Gly-Phe-Glu-NH2 (I) and the structurally related open chain analogs H-Tyr-D-Nle-Gly-Phe-Gln-NH2 (II) and H-Tyr-D-Lys(For)-Gly-Phe-Abu-NH2 (III) were tested in mu and delta opioid receptor-representative binding assays and bioassays. Whereas both linear analogs showed a pronounced preference for mu receptors over delta receptors, the conformationally restricted cyclic peptide I was found to be unselective. This finding represents the first reported example of a peptide cyclization resulting in a loss of receptor selectivity. From this and earlier studies, it was concluded that the receptor selectivity of cyclized peptide analogs relative to that of their linear correlates may depend on the size and relative rigidity of their ring structures.


Recent advances in measurement of amylase activity--a comparative study.
We evaluated four kinetic amylase procedures with respect to kinetics, analytical range, blank rates, reagent stability, reagent impurities, interfering substances, and intrinsic sensitivities. Each of the methods is shown to have its own unique advantages and disadvantages. A preliminary discussion of some alternative methods, in which glycosidic p-nitrophenyl alpha-oligosaccharides are substrates, is included.


An investigation of the prevalence of psychological morbidity in burn-injured patients.
Research on the psychological impact of burn injuries has concentrated on major burns, while small burns have been largely neglected. In a prospective study, 45 patients with burn injuries ranging from 1 per cent or less up to 40 per cent total body surface area were assessed using semi-structured interviews within 2 weeks of sustaining the burn, and followed-up at approximately 3 months postburn to investigate the prevalence of mental health problems. The prevalence of clinically significant levels of anxiety, intrusions and avoidance remained similar at 2 weeks and 3 months postburn, however, the prevalence of depression and Post Traumatic Stress Disorder (PTSD) increased 6- and 4-times, respectively, by 3 months. Patients with small burn injuries of 1 per cent or less also experienced clinically significant levels of psychological difficulties postburn. The implications for the identification of patients at risk of future psychological morbidity are discussed.


Interferon induction by measles virus.
Interferon induction in BSC-1 cells by measles virus isolates previously found to be interferon inducing (IF+) or interferon noninducing (IF-) was studied in different cell types. Lack of induction by the IF- viruses was not due to an inhibitory factor since BSC-1 cells coinfected with IF+ and IF- stocks produced interferon levels similar to those infected with IF+ stocks alone. Various tests indicated that the phenotypic expression of interferon induction by these isolates was dependent on an infectious virus genome, the cell type tested, and the passage history of the virus. In contrast to the in vitro results, the IF- phenotype was stable in vivo, whereas passage of the IF+ virus resulted in selection against the IF+ phenotype. The phenotypic expression of interferon induction by measles virus was, therefore, controlled by complex interactions between virus and host cell factors exerted both in vivo and in vitro.


MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs.
The antioxidant activity of genistein is associated with preventing atherosclerosis; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to ox-LDL (50mg/L) for another 24h. Results showed that genistein restrained reactive oxygen species (ROS) and malondialdehyde (MDA) production, and ameliorated the inhibitory effect on superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) activity elicited by ox-LDL stimulation. The effects of genistein were correlated with the upregulation of sirtuin-1 via inhibiting miR-34a, and were abolished by sirtuin-1 siRNA or miR-34a mimic. Moreover, the antioxidation of genistein was associated with miR-34a/sirtuin-1-mediated nuclear translocation and deacetylation of foxo3a, accompanying with the enhanced expressions of MnSOD and CAT. The present study suggests that miR-34a/sirtuin-1/foxo3a might play an important role in genistein reversing ox-LDL-induced oxidative damage in HUVECs.


Stabilizing leaning postures with feedback controlled functional neuromuscular stimulation after trunk paralysis.
Spinal cord injury (SCI) can cause paralysis of trunk and hip musculature that negatively impacts seated balance and ability to lean away from an upright posture and interact fully with the environment. Constant levels of electrical stimulation of peripheral nerves can activate typically paralyzed muscles and aid in maintaining a single upright seated posture. However, in the absence of a feedback controller, such seated postures and leaning motions are inherently unstable and unable to respond to perturbations. Three individuals with motor complete SCI who had previously received a neuroprosthesis capable of activating the hip and trunk musculature volunteered for this study. Subject-specific muscle synergies were identified through system identification of the lumbar moments produced via neural stimulation. Synergy-based calculations determined the real-time stimulation parameters required to assume leaning postures. When combined with a proportional, integral, derivative (PID) feedback controller and an accelerometer to infer trunk orientation, all individuals were able to assume non-erect postures of 30-40° flexion and 15° lateral bending. Leaning postures increased forward reaching capabilities by 10.2, 46.7, and 16 cm respectively for each subject when compared with no stimulation. Additionally, the leaning controllers were able to resist perturbations of up to 90 N, and all subjects perceived the leaning postures as moderately to very stable. Implementation of leaning controllers for neuroprostheses have the potential of expanding workspaces, increasing independence, and facilitating activities of daily living for individuals with paralysis.


Direct segmentation of brain white matter tracts in diffusion MRI.
The brain white matter consists of a set of tracts that connect distinct regions of the brain. Segmentation of these tracts is often needed for clinical and research studies. Diffusion-weighted MRI offers unique contrast to delineate these tracts. However, existing segmentation methods rely on intermediate computations such as tractography or estimation of fiber orientation density. These intermediate computations, in turn, entail complex computations that can result in unnecessary errors. Moreover, these intermediate computations often require dense multi-shell measurements that are unavailable in many clinical and research applications. As a result, current methods suffer from low accuracy and poor generalizability. Here, we propose a new deep learning method that segments these tracts directly from the diffusion MRI data, thereby sidestepping the intermediate computation errors. Our experiments show that this method can achieve segmentation accuracy that is on par with the state of the art methods (mean Dice Similarity Coefficient of 0.826). Compared with the state of the art, our method offers far superior generalizability to undersampled data that are typical of clinical studies and to data obtained with different acquisition protocols. Moreover, we propose a new method for detecting inaccurate segmentations and show that it is more accurate than standard methods that are based on estimation uncertainty quantification. The new methods can serve many critically important clinical and scientific applications that require accurate and reliable non-invasive segmentation of white matter tracts.


The laboratory management of a medicolegal specimen.
The medicolegal specimen refers to any material, biologic or nonbiologic, that is analyzed by the laboratory as part of an investigative procedure, the results of which may be presented as evidence in a court of law. The medicolegal specimen is an example of physical evidence and has an intrinsic credibility based on the reliability of the person handling it, the reliability of methods of laboratory analysis and the reliability of testimony with relationship to the interpretations of the findings. Aspects of specimen integrity, re: chain of custody, sample collection, specifications for samples and utilization of samples, are outlined. The responsibilities for the management of the specimen are defined and discussed with suggested guidelines recommended.


N-Trans-p-Coumaroyltyramine Enhances Indomethacin- and Diclofenac-induced Apoptosis Through Endoplasmic Reticulum Stress-dependent Mechanism in MCF-7 Cells.
The anticancer potential of indomethacin and diclofenac has been reported against several types of cancer cells. In this study, we investigated the enhancement effect of a coumaric acid derivative found in some Piper plants, N-trans-p-coumaroyltyramine (TCT) on indomethacin and diclofenac cytotoxicity in breast cancer cells. MCF-7 and mitoxantrone-resistant MCF-7 (MCF-7/MX) cancer cells were treated with indomethacin or diclofenac in the presence of TCT for 48 h. Cell viability, apoptosis, mitochondrial function and signaling proteins were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Hoechst 33342, tetramethyl-rhodamine-ethyl-ester and western blot analysis, respectively. Combination treatment resulted in significant reduction of cell viability and mitochondrial membrane potential, whereas the ratio of BCL2-associated X, apoptosis regulator to BCL2 apoptosis regulator, and apoptosis increased. The enhancing effect of TCT was related to reduced nuclear factor-erythroid factor 2-related factor 2/heme oxygenase-1 expression, and increased activation of the protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2 alpha/activating transcription factor 4/C/EBP homologous protein signaling pathways. TCT in combination with indomethacin or diclofenac promoted endoplasmic reticulum stress-dependent apoptosis in breast cancer cells.


MLKL Mediated Necroptosis Accelerates JEV-Induced Neuroinflammation in Mice.
Japanese encephalitis virus (JEV) is the most prevalent cause of viral encephalitis in Asia and the western Pacific. Neuronal death caused by JEV infection and inflammation induced cytotoxicity leads to progression and deterioration of Japanese encephalitis (JE). Mixed-lineage kinase domain-like protein (MLKL) mediated necroptosis is a newly discovered pathway of programmed cell death and participates in many inflammatory diseases. In this study, we demonstrated for the first time that necroptosis was involved in the neuronal loss during JE via immune-electron microscopy and immunochemistry. The expression of MLKL in neurons was upregulated in presence of JEV infection in vitro and in vivo. Deletion of MLKL alleviated the progression of JE and decreased the level of inflammatory cytokines in mice model. Taken together, this study provides evidence for the participation of necroptosis in the pathogenesis of JEV infection.


[Study on difference of liver toxicity and its molecular mechanisms caused by Tripterygium wilfordii multiglycoside and equivalent amount of triptolid in rats].
Tripterygium wilfordii multiglycoside( GTW),an extract derived from T. wilfordii,has been used for rheumatoid arthritis and other immune diseases in China. However its potential hepatotoxicity has not been investigated completely. Firstly,the content of triptolid( TP) in GTW was 0. 008% confirmed by a LC method. Then after oral administration of GTW( 100,150 mg·kg-1) and TP( 12 μg·kg-1) in female Wistar rats for 24 h,it was found that 150 mg·kg-1 GTW showed more serious acute liver injury than 12 μg·kg-1 TP,with the significantly increased lever of serum ALT,AST,TBA,TBi L,TG and bile duct hyperplasia even hepatocyte apoptosis. The expression of mRNA and proteins of liver bile acid transporters such as BSEP,MRP2,NTCP and OATP were down-regulated significantly by GTW to inhibit bile acid excretion and absorption,resulting in cholestatic liver injury. Moreover,GTW was considered to be involved in hepatic oxidative stress injury,although it down-regulated SOD1 and GPX-1 mRNA expression without significant difference in MDA and GSH levels. In vitro,we found that TP was the main toxic component in GTW,which could inhibit cell viability up to 80% in Hep G2 and LO2 cells at the dose of 0. 1 μmol·L-1. Next a LC-MS/MS method was used to detect the concentration of triptolid in plasma from rats,interestingly,we found that the content of TP in GTW was always higher than in the same amount of TP,suggesting the other components in GTW may affect the TP metabolism. Finally,we screened the substrate of p-glycoprotein( p-gp) in Caco-2 cells treated with components except TP extrated from GTW,finding that wilforgine,wilforine and wilfordine was the substrate of p-gp. Thus,we speculated that wilforgine,wilforine and wilfordine may competitively inhibit the excretion of TP to bile through p-gp,leading to the enhanced hepatotoxity caused by GTW than the same amount of TP.


Serum markers of chronic dehydration are associated with saliva spinability.
Findings of a relationship between saliva and dehydration have been observed, but the precise nature of these relationships is unclear and no evidence of a direct link has been found. In particular, no study reports a relationship between chronic dehydration and saliva conditions in community-dwelling older adults. This study aimed to identify whether salivary conditions are sensitive to body hydration markers in an elderly population. A total of 403 subjects aged 76 years participated in the study. Stimulated saliva flow rate and spinability of saliva were measured. In addition, determinations of serum levels of uric acid, blood urea nitrogen (BUN), creatinine, sodium and potassium were made. Dehydration was defined as uric acid >/= 7 mg dL(-1) according to the standard value. The salivary spinability were significantly associated with the concentration of uric acid (OR=2.06, P=0.044) according to multiple logistic regression analysis. In addition, after adjusting for gender, the uric acid concentration and the salivary spinability was significantly associated with BUN, potassium and creatinine levels. The subjects with high uric acid levels (>/= 7 mg dL(-1)) had the most elastic saliva. Both BUN and serum creatinine are the most commonly used indicators of renal function. Therefore, our findings might demonstrate that older adults who are dehydrated showed highly elastic saliva, which was associated with renal function. In conclusion, this study suggests that there is a significant relationship between chronic dehydration status and salivary spinability level.


Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.
Despite surgical removal of tumors with portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients, early recurrence tends to occur, and overall survival (OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization (TACE); subcutaneous administration of interferon-alpha (IFN-α) and intra-arterial infusion of 5-fluorouracil (5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy (5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.


Mechanism of antioxidant action of natural phenolics on scallop (Argopecten irradians) adductor muscle during drying process.
Lipid hydrolysis and oxidation occurred in Argopecten irradians adductor muscle during hot air drying. Using an in vivo imaging system, we found that antioxidants of bamboo leaves (AOB) could diffuse into the adductor muscle upon marinating. Both tea polyphenols (TP) and AOB efficiently retarded lipid oxidation but had a slight effect on lipid hydrolysis during drying process. The in situ antioxidant mechanisms of AOB as well as TP were revealed, including quenching of free radicals detected by electron spin resonance, chelating metal ions determined by confocal laser scanning microscopy and inhibiting lipoxygenase. Less than 8% of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in AOB and TP marinated adductor muscle were decreased compared to more than 28% decrease in control adductor muscle during the drying process. Overall, these natural antioxidants, TP and AOB, efficiently maintained high nutritive value of adductor muscle, especially, their lipid quality.


Microtubule-induced nuclear envelope fluctuations control chromatin dynamics in Drosophila embryos.
Nuclear shape is different in stem cells and differentiated cells and reflects important changes in the mechanics of the nuclear envelope (NE). The current framework emphasizes the key role of the nuclear lamina in nuclear mechanics and its alterations in disease. Whether active stress controls nuclear deformations and how this stress interplays with properties of the NE to control NE dynamics is unclear. We address this in the early Drosophila embryo, in which profound changes in NE shape parallel the transcriptional activation of the zygotic genome. We show that microtubule (MT) polymerization events produce the elementary forces necessary for NE dynamics. Moreover, large-scale NE deformations associated with groove formation require concentration of MT polymerization in bundles organized by Dynein. However, MT bundles cannot produce grooves when the farnesylated inner nuclear membrane protein Kugelkern (Kuk) is absent. Although it increases stiffness of the NE, Kuk also stabilizes NE deformations emerging from the collective effect of MT polymerization forces concentrated in bundles. Finally, we report that MT-induced NE deformations control the dynamics of chromatin and its organization at steady state. Thus, the NE is a dynamic organelle, fluctuations of which increase chromatin dynamics. We propose that such mechanical regulation of chromatin dynamics by MTs might be important for gene regulation.


Identifying Active Sites for Parasitic Reactions at the Cathode-Electrolyte Interface.
Nickel-rich transition metal oxides are the most promising high-voltage and high-capacity cathode materials for high-energy-density lithium batteries. Improving the chemical/electrochemical stability of the cathode-electrolyte interface has been the major technical focus to enable this class of cathode materials. In this work, LiCoO2 is adopted as the model cathode material to investigate the active sites for parasitic reactions between the delithiated cathode and the nonaqueous electrolyte. Both ab initio calculations and experimental results clearly show that the partially coordinated transition metal atoms at the surface are responsible for the parasitic reactions at the cathode-electrolyte interface. This finding lays out fundamental support for rational interfacial engineering to further improve the life and safety characteristics of nickel-rich cathode materials.


The heparin-binding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival.
The survival of cultured chick sympathetic neurons and the outgrowth of neurites were stimulated by the basement membrane protein laminin coated onto polyornithine culture substrates. The survival-potentiating activity was dependent on the presence of nerve growth factor. Both effects of laminin could be completely inhibited by affinity-purified antibodies against laminin fragment 3, the product of a limited proteolysis that corresponds to the heparin-binding globular domain at the end of the long arm of the laminin molecule. Antibodies against other laminin fragments were inactive, including those against previously determined cell-binding domains. A large laminin fragment, E8, was produced by brief elastase digestion and shown to consist of fragment 3 and an adjacent rod-like structure. Although lacking the cell binding domains, fragment E8 potentiated both neuronal survival and neurite outgrowth, and these effects could be blocked by antibodies against fragment 3. Weak survival and neurite potentiating activity was also detected in another fragment corresponding to the short arms of laminin, but as these effects were not inhibited by any of the antibodies tested they probably arose de novo during proteolysis. The heparin-binding domain of laminin is therefore responsible for its effects on neurons.


A symptomatic lumbosacral perineural cyst -A case report-.
Lumbosacral perineural cysts are formed by the arachnoid membrane of the nerve root at the lumbosacral level. Most of these cysts are asymptomatic and are found incidentally during computed tomography (CT) or magnetic resonance imaging (MRI) for other causes of chronic lower back pain. This type of cyst requires a differential diagnosis to distinguish it from other causes of radiating pain and neurological symptoms. In the present case, a symptomatic lumbosacral perineural cyst was found, and pain relief was achieved by non-surgical treatment. A lumbosacral perineural cyst was identified from a differential diagnosis of a lumbar disc disorder that presented as radiating pain and neurological symptoms.